Apomorphine (APO) and N-n-propylnorapomorphine (NPA) show definite promise as clinically useful antiparkinsonian agents. Of additional interest are recent reports that APO may be efficacious in the management of dyskinetic conditions such as Huntington's chorea and tardive dyskinesia, and in treating Gilles de la Tourette's syndrome. Paradoxical, yet real effectiveness is attributed to the use of APO in the treatment of schizophrenia and haloperidol-induced neurodysleptic syndrome. These reports should promote further interest in the basic chemistry, pharmacology, and clinical utility of apomorphine and its analogs. On the negative side, APO's poor oral activity (due to "first-pass" effect first demonstrated in our laboratories), its short biological half-life, its toxicity (especially azotemia), and its difficult analysis in biological fluids, inhibit the wide-spread testing of APO in the clinic. An interdisciplinary program embracing basic chemistry and pharmacology/toxicology has continued to study these problems and their possible interrelationships. Findings during the reviewed period include thorough study of the bioavailability of APO and NPA in mice and correlation of circulating levels of drugs to a behavioral test, stereotyped cage climbing. This work serves as a prelude for the evaluation of an extensive series of prodrugs of APO. Some diesters and a cyclic ester (carbonate) of APO have been prepared and pharmacologically evaluated. One compound, the 0,0-diphenylacetyl ester, appears to show particularly promising prolonged activity in vivo. This work may lead to promising orally active analogs of APO and NPA. The APO-induced azotemia rabbit model has been more fully characterized and future experiments should permit study of the mechanism of this most troublesome side-effect of APO. Continued investigations of the HPLC analysis of APO and NPA suggest that methods employing either electrochemical or fluorescence detection may provide the sensitivity necessary for biodisposition experiments in man.